Objective: The overall goal of this project is to identify strategies to reduce lung cancer incidence and mortality. Specific objectives are to 1) establish a biologic specimen bank and data bank that can be used for the validation and refinement of potential early markers of lung cancer and 2) establish a cohort for the study of environmental (including dietary) and genetic risk factors for lung cancer. Background: Lung cancer is the leading cause of cancer death in the U.S. While relative survival rates for localized disease are dramatically better than for nonlocalized disease, most patients are not diagnosed early enough for present therapies to be effective, and early detection by screening with conventional modalities (i.e., chest x-ray and/or sputum cytology) has not been shown to be beneficial. Potential strategies to reduce the incidence and mortality of lung cancer include new methods of early detection and identification and alteration of etiologic factors. Methods: Miners in the Yunnan Tin Corporation have an extraordinary rate of lung cancer due to exposure to radon, arsenic, and tobacco. Over 7,000 high-risk miners (40+ years old with 10+ years of underground and/or smelting experience) have been the target of an annual lung cancer screening program (CXR and sputum cytology) for the past 20+ years. Since 1992, sputum samples have been collected and stored annually for future early marker research, and new cases of lung cancer ascertained. Prediagnostic sputum and other biologic samples will be analyzed for potential early markers (e.g., molecular or monoclonal antibody markers) utilizing a nested case-control approach. Progress: Results of analyses in 57 cases from 1992 showed that Mab detection of hnRNP tumor-associated antigens expressed by sputum cells was 2 to 3-fold more sensitive than routine screening methods but somewhat less specific. Lab analyses are in progress to evaluate Mabs, microsatellite markers, and p53 in tumor and prediagnostic sputum specimens. Epidemiologic analyses are also underway to evaluate the relation of occupational and dietary exposures as well as medical conditions to lung cancer.